ID NTCP_HUMAN Reviewed; 349 AA. AC Q14973; B9EGB6; Q2TU29; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 03-MAY-2023, entry version 184. DE RecName: Full=Hepatic sodium/bile acid cotransporter; DE AltName: Full=Cell growth-inhibiting gene 29 protein; DE AltName: Full=Na(+)/bile acid cotransporter; DE AltName: Full=Na(+)/taurocholate transport protein; DE AltName: Full=Sodium/taurocholate cotransporting polypeptide {ECO:0000303|PubMed:14660639, ECO:0000303|PubMed:24867799}; DE Short=NTCP {ECO:0000303|PubMed:14660639, ECO:0000303|PubMed:24867799}; DE AltName: Full=Solute carrier family 10 member 1; DE Short=SLC10A1 {ECO:0000303|PubMed:14660639, ECO:0000303|PubMed:24867799}; GN Name=SLC10A1; Synonyms=NTCP; ORFNames=GIG29; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORT ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RC TISSUE=Liver; RX PubMed=8132774; DOI=10.1172/jci117091; RA Hagenbuch B., Meier P.J.; RT "Molecular cloning, chromosomal localization, and functional RT characterization of a human liver Na+/bile acid cotransporter."; RL J. Clin. Invest. 93:1326-1331(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kim J.W.; RT "Identification of a human cell growth inhibition gene."; RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, TRANSPORT ACTIVITY, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=9458785; DOI=10.1152/ajpgi.1998.274.1.g157; RA Craddock A.L., Love M.W., Daniel R.W., Kirby L.C., Walters H.C., Wong M.H., RA Dawson P.A.; RT "Expression and transport properties of the human ileal and renal sodium- RT dependent bile acid transporter."; RL Am. J. Physiol. 274:G157-G169(1998). RN [6] RP TISSUE SPECIFICITY. RX PubMed=11031103; DOI=10.1006/geno.2000.6329; RA Shiao T., Iwahashi M., Fortune J., Quattrochi L., Bowman S., Wick M., RA Qadri I., Simon F.R.; RT "Structural and functional characterization of liver cell-specific activity RT of the human sodium/taurocholate cotransporter."; RL Genomics 69:203-213(2000). RN [7] RP TISSUE SPECIFICITY. RX PubMed=12409283; DOI=10.1152/ajpendo.00257.2002; RA Ugele B., St-Pierre M.V., Pihusch M., Bahn A., Hantschmann P.; RT "Characterization and identification of steroid sulfate transporters of RT human placenta."; RL Am. J. Physiol. 284:E390-E398(2003). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS THR-223; THR-279 AND GLU-314, RP VARIANT FHCA2 PHE-267, CHARACTERIZATION OF VARIANT FHCA2 PHE-267, RP CHARACTERIZATION OF VARIANTS THR-279 AND GLU-314, TRANSPORT ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=14660639; DOI=10.1074/jbc.m305782200; RA Ho R.H., Leake B.F., Roberts R.L., Lee W., Kim R.B.; RT "Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting RT polypeptide (SLC10A1) reveals a domain critical for bile acid substrate RT recognition."; RL J. Biol. Chem. 279:7213-7222(2004). RN [9] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HEPATITIS B VIRUS RP LARGE ENVELOPE PROTEIN. RX PubMed=23150796; RA Yan H., Zhong G., Xu G., He W., Jing Z., Gao Z., Huang Y., Qi Y., Peng B., RA Wang H., Fu L., Song M., Chen P., Gao W., Ren B., Sun Y., Cai T., Feng X., RA Sui J., Li W.; RT "Sodium taurocholate cotransporting polypeptide is a functional receptor RT for human hepatitis B and D virus."; RL Elife 1:E00049-E00049(2012). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, VARIANT FHCA2 HIS-252, CHARACTERIZATION OF RP VARIANT FHCA2 HIS-252, TRANSPORT ACTIVITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=24867799; DOI=10.1002/hep.27240; RA Vaz F.M., Paulusma C.C., Huidekoper H., de Ru M., Lim C., Koster J., RA Ho-Mok K., Bootsma A.H., Groen A.K., Schaap F.G., Oude Elferink R.P., RA Waterham H.R., Wanders R.J.; RT "Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: RT conjugated hypercholanemia without a clear clinical phenotype."; RL Hepatology 61:260-267(2015). RN [11] RP FUNCTION, TRANSPORT ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=34060352; DOI=10.1177/24725552211017500; RA Floerl S., Kuehne A., Geyer J., Brockmoeller J., Tzvetkov M.V., Hagos Y.; RT "Functional and Pharmacological Comparison of Human and Mouse RT Na+/Taurocholate Cotransporting Polypeptide (NTCP)."; RL SLAS Discovery 26:1055-1064(2021). RN [12] RP FUNCTION. RX PubMed=33222321; DOI=10.1002/hep.31651; RA Kunst R.F., Verkade H.J., Oude Elferink R.P.J., van de Graaf S.F.J.; RT "Targeting the Four Pillars of Enterohepatic Bile Salt Cycling; Lessons RT From Genetics and Pharmacology."; RL Hepatology 73:2577-2585(2021). RN [13] RP ASSOCIATION OF VARIANT PHE-267 WITH RESISTANCE TO CHRONIC HEPATITIS B. RX PubMed=25418280; DOI=10.1002/hep.27608; RA Peng L., Zhao Q., Li Q., Li M., Li C., Xu T., Jing X., Zhu X., Wang Y., RA Li F., Liu R., Zhong C., Pan Q., Zeng B., Liao Q., Hu B., Hu Z.X., RA Huang Y.S., Sham P., Liu J., Xu S., Wang J., Gao Z.L., Wang Y.; RT "The p.Ser267Phe variant in SLC10A1 is associated with resistance to RT chronic hepatitis B."; RL Hepatology 61:1251-1260(2015). RN [14] RP VARIANT FHCA2 PHE-267, AND INVOLVEMENT IN FHCA2. RX PubMed=27882152; DOI=10.3892/etm.2016.3752; RA Deng M., Mao M., Guo L., Chen F.P., Wen W.R., Song Y.Z.; RT "Clinical and molecular study of a pediatric patient with sodium RT taurocholate cotransporting polypeptide deficiency."; RL Exp. Ther. Med. 12:3294-3300(2016). RN [15] RP VARIANT FHCA2 PHE-267. RX PubMed=28283843; DOI=10.1007/s10545-017-0031-9; RA Van Herpe F., Waterham H.R., Adams C.J., Mannens M., Bikker H., Vaz F.M., RA Cassiman D.; RT "NTCP deficiency and persistently raised bile salts: an adult case."; RL J. Inherit. Metab. Dis. 40:313-315(2017). RN [16] RP VARIANTS FHCA2 THR-88 AND PHE-267. RX PubMed=29290974; DOI=10.18632/oncotarget.22503; RA Qiu J.W., Deng M., Cheng Y., Atif R.M., Lin W.X., Guo L., Li H., Song Y.Z.; RT "Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: RT Identification of a novel SLC10A1 mutation in two unrelated infants RT presenting with neonatal indirect hyperbilirubinemia and remarkable RT hypercholanemia."; RL Oncotarget 8:106598-106607(2017). RN [17] RP VARIANT PHE-267, AND INVOLVEMENT IN FHCA2. RX PubMed=28835676; DOI=10.1038/s41598-017-07012-2; RA Liu R., Chen C., Xia X., Liao Q., Wang Q., Newcombe P.J., Xu S., Chen M., RA Ding Y., Li X., Liao Z., Li F., Du M., Huang H., Dong R., Deng W., Wang Y., RA Zeng B., Pan Q., Jiang D., Zeng H., Sham P., Cao Y., Maxwell P.H., RA Gao Z.L., Peng L., Wang Y.; RT "Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of RT hypercholanemia and implications for personalized medicine."; RL Sci. Rep. 7:9214-9214(2017). RN [18] RP VARIANTS FHCA2 ARG-199 AND PHE-267. RX PubMed=31661128; DOI=10.3892/mmr.2019.10763; RA Li H., Deng M., Guo L., Qiu J.W., Lin G.Z., Long X.L., Xiao X.M., RA Song Y.Z.; RT "Clinical and molecular characterization of four patients with NTCP RT deficiency from two unrelated families harboring the novel SLC10A1 variant RT c.595A>C (p.Ser199Arg)."; RL Mol. Med. Report. 20:4915-4924(2019). RN [19] RP CHARACTERIZATION OF VARIANTS CYS-21; THR-39; LEU-41; THR-64; THR-73; RP THR-88; PRO-138; MET-159; GLN-180; GLU-190; THR-232; LEU-234; PHE-241; RP TRP-249; CYS-252; SER-252; SER-258; THR-279 AND GLU-293. RX PubMed=32101444; DOI=10.1021/acs.molpharmaceut.9b01200; RA Russell L.E., Zhou Y., Lauschke V.M., Kim R.B.; RT "In vitro functional characterization and in silico prediction of rare RT genetic variation in the bile acid and drug transporter, Na+-taurocholate RT cotransporting polypeptide (NTCP, SLC10A1)."; RL Mol. Pharm. 17:1170-1181(2020). RN [20] RP VARIANTS FHCA2 THR-88; ARG-199 AND PHE-267. RX PubMed=34369070; DOI=10.1111/liv.15031; RA Deng L.J., Ouyang W.X., Liu R., Deng M., Qiu J.W., Yaqub M.R., Raza M.A., RA Lin W.X., Guo L., Li H., Chen F.P., Ouyang Y., Huang Y.G., Huang Y.J., RA Long X.L., Huang X.L., Li S.J., Song Y.Z.; RT "Clinical characterization of NTCP deficiency in paediatric patients: A RT case-control study based on SLC10A1 genotyping analysis."; RL Liver Int. 41:2720-2728(2021). CC -!- FUNCTION: As a major transporter of conjugated bile salts from plasma CC into the hepatocyte, it plays a key role in the enterohepatic CC circulation of bile salts necessary for the solubilization and CC absorption of dietary fat and fat-soluble vitamins (PubMed:8132774, CC PubMed:14660639, PubMed:24867799, PubMed:34060352). It is strictly CC dependent on the extracellular presence of sodium (PubMed:8132774, CC PubMed:14660639, PubMed:24867799, PubMed:34060352). It exhibits broad CC substrate specificity and transports various bile acids, such as CC taurocholate, cholate, as well as non-bile acid organic compounds, such CC as estrone sulfate (PubMed:14660639, PubMed:34060352). Works CC collaboratively with the ileal transporter (NTCP2), the organic solute CC transporter (OST), and the bile salt export pump (BSEP), to ensure CC efficacious biological recycling of bile acids during enterohepatic CC circulation (PubMed:33222321). {ECO:0000269|PubMed:14660639, CC ECO:0000269|PubMed:24867799, ECO:0000269|PubMed:34060352, CC ECO:0000269|PubMed:8132774, ECO:0000303|PubMed:33222321}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis B CC virus. {ECO:0000269|PubMed:23150796}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + taurocholate(out) = 2 Na(+)(in) + CC taurocholate(in); Xref=Rhea:RHEA:71875, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:36257; Evidence={ECO:0000269|PubMed:14660639, CC ECO:0000269|PubMed:9458785}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cholate(out) + 2 Na(+)(out) = cholate(in) + 2 Na(+)(in); CC Xref=Rhea:RHEA:71911, ChEBI:CHEBI:29101, ChEBI:CHEBI:29747; CC Evidence={ECO:0000269|PubMed:14660639}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone 3-sulfate(out) + 2 Na(+)(out) = estrone 3-sulfate(in) CC + 2 Na(+)(in); Xref=Rhea:RHEA:71083, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:60050; Evidence={ECO:0000269|PubMed:14660639, CC ECO:0000269|PubMed:9458785}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + taurochenodeoxycholate(out) = 2 Na(+)(in) + CC taurochenodeoxycholate(in); Xref=Rhea:RHEA:71923, ChEBI:CHEBI:9407, CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + tauroursodeoxycholate(out) = 2 Na(+)(in) + CC tauroursodeoxycholate(in); Xref=Rhea:RHEA:71927, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:132028; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glycocholate(out) + 2 Na(+)(out) = glycocholate(in) + 2 CC Na(+)(in); Xref=Rhea:RHEA:71935, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:29746; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + tauronorcholate(out) = 2 Na(+)(in) + CC tauronorcholate(in); Xref=Rhea:RHEA:71915, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:191405; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + taurodeoxycholate(out) = 2 Na(+)(in) + CC taurodeoxycholate(in); Xref=Rhea:RHEA:72087, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:36261; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + tauroallocholate(out) = 2 Na(+)(in) + CC tauroallocholate(in); Xref=Rhea:RHEA:51840, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:191406; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + taurohyodeoxycholate(out) = 2 Na(+)(in) + CC taurohyodeoxycholate(in); Xref=Rhea:RHEA:72167, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:191407; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + taurohyocholate(out) = 2 Na(+)(in) + CC taurohyocholate(in); Xref=Rhea:RHEA:72171, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:58874; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + tauro-beta-muricholate(out) = 2 Na(+)(in) + CC tauro-beta-muricholate(in); Xref=Rhea:RHEA:72179, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:133064; Evidence={ECO:0000250|UniProtKB:O97736}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.3 uM for taurocholate {ECO:0000269|PubMed:8132774}; CC KM=10 uM for taurocholate {ECO:0000269|PubMed:9458785}; CC KM=7.5 uM for taurocholate {ECO:0000269|PubMed:14660639}; CC KM=15 uM for taurocholate {ECO:0000269|PubMed:24867799}; CC KM=12 uM for cholate {ECO:0000269|PubMed:14660639}; CC KM=60 uM for estrone 3-sulfate {ECO:0000269|PubMed:9458785}; CC KM=27 uM for estrone 3-sulfate {ECO:0000269|PubMed:14660639}; CC KM=67 uM for estrone 3-sulfate {ECO:0000269|PubMed:34060352}; CC Vmax=333 pmol/min/mg enzyme with taurocholate as substrate CC {ECO:0000269|PubMed:9458785}; CC Vmax=415 pmol/min/mg enzyme with taurocholate as substrate CC {ECO:0000269|PubMed:14660639}; CC Vmax=139 pmol/min/mg enzyme with cholate as substrate CC {ECO:0000269|PubMed:14660639}; CC Vmax=111 pmol/min/mg enzyme with estrone 3-sulfate as substrate CC {ECO:0000269|PubMed:9458785}; CC Vmax=68 pmol/min/mg enzyme with estrone 3-sulfate as substrate CC {ECO:0000269|PubMed:14660639}; CC Vmax=1060 pmol/min/mg enzyme with estrone 3-sulfate as substrate CC {ECO:0000269|PubMed:34060352}; CC Vmax=130 pmol/min/mg enzyme with taurocholate as substrate CC {ECO:0000269|PubMed:24867799}; CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis B virus large CC envelope protein. {ECO:0000269|PubMed:23150796}. CC -!- INTERACTION: CC Q14973; O95870: ABHD16A; NbExp=3; IntAct=EBI-3923031, EBI-348517; CC Q14973; Q9ULC5: ACSL5; NbExp=3; IntAct=EBI-3923031, EBI-2876927; CC Q14973; Q9NRZ7: AGPAT3; NbExp=3; IntAct=EBI-3923031, EBI-2803601; CC Q14973; Q8N6S5: ARL6IP6; NbExp=3; IntAct=EBI-3923031, EBI-2808844; CC Q14973; P07306: ASGR1; NbExp=3; IntAct=EBI-3923031, EBI-1172335; CC Q14973; Q99437: ATP6V0B; NbExp=3; IntAct=EBI-3923031, EBI-3904417; CC Q14973; O95393: BMP10; NbExp=3; IntAct=EBI-3923031, EBI-3922513; CC Q14973; P06681: C2; NbExp=3; IntAct=EBI-3923031, EBI-2835920; CC Q14973; P07357: C8A; NbExp=3; IntAct=EBI-3923031, EBI-9021639; CC Q14973; Q9BXR6: CFHR5; NbExp=3; IntAct=EBI-3923031, EBI-11579371; CC Q14973; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-3923031, EBI-12256978; CC Q14973; Q96MX0: CMTM3; NbExp=3; IntAct=EBI-3923031, EBI-7247651; CC Q14973; Q5RI15: COX20; NbExp=3; IntAct=EBI-3923031, EBI-2834035; CC Q14973; Q07325: CXCL9; NbExp=3; IntAct=EBI-3923031, EBI-3911467; CC Q14973; P00387: CYB5R3; NbExp=3; IntAct=EBI-3923031, EBI-1046040; CC Q14973; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-3923031, EBI-398977; CC Q14973; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-3923031, EBI-12831978; CC Q14973; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-3923031, EBI-11337888; CC Q14973; Q96D05-2: FAM241B; NbExp=3; IntAct=EBI-3923031, EBI-12118888; CC Q14973; Q96IV6: FAXDC2; NbExp=3; IntAct=EBI-3923031, EBI-12142299; CC Q14973; P37268: FDFT1; NbExp=3; IntAct=EBI-3923031, EBI-714550; CC Q14973; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-3923031, EBI-12175685; CC Q14973; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-3923031, EBI-713304; CC Q14973; P01350: GAST; NbExp=3; IntAct=EBI-3923031, EBI-3436637; CC Q14973; Q9NZC3: GDE1; NbExp=3; IntAct=EBI-3923031, EBI-2833330; CC Q14973; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-3923031, EBI-6166686; CC Q14973; O14653: GOSR2; NbExp=3; IntAct=EBI-3923031, EBI-4401517; CC Q14973; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-3923031, EBI-11955647; CC Q14973; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-3923031, EBI-13345167; CC Q14973; Q6IBB0: IFITM2; NbExp=3; IntAct=EBI-3923031, EBI-12167419; CC Q14973; Q01628: IFITM3; NbExp=3; IntAct=EBI-3923031, EBI-7932862; CC Q14973; Q7Z4F1: LRP10; NbExp=3; IntAct=EBI-3923031, EBI-2830349; CC Q14973; P48449: LSS; NbExp=3; IntAct=EBI-3923031, EBI-3930711; CC Q14973; P21145: MAL; NbExp=3; IntAct=EBI-3923031, EBI-3932027; CC Q14973; Q13021: MALL; NbExp=3; IntAct=EBI-3923031, EBI-750078; CC Q14973; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-3923031, EBI-2858252; CC Q14973; P11836: MS4A1; NbExp=3; IntAct=EBI-3923031, EBI-2808234; CC Q14973; A6NDP7: MYADML2; NbExp=3; IntAct=EBI-3923031, EBI-17641390; CC Q14973; Q99519: NEU1; NbExp=3; IntAct=EBI-3923031, EBI-721517; CC Q14973; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-3923031, EBI-10317425; CC Q14973; Q9P0S3: ORMDL1; NbExp=3; IntAct=EBI-3923031, EBI-1054848; CC Q14973; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-3923031, EBI-11075081; CC Q14973; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-3923031, EBI-721750; CC Q14973; Q7RTS5: OTOP3; NbExp=3; IntAct=EBI-3923031, EBI-12853910; CC Q14973; I3L0A0: PEDS1-UBE2V1; NbExp=3; IntAct=EBI-3923031, EBI-12213001; CC Q14973; Q9Y5Y5: PEX16; NbExp=3; IntAct=EBI-3923031, EBI-981985; CC Q14973; Q99640-2: PKMYT1; NbExp=3; IntAct=EBI-3923031, EBI-12257782; CC Q14973; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-3923031, EBI-8636004; CC Q14973; Q9NTJ5: SACM1L; NbExp=3; IntAct=EBI-3923031, EBI-3917235; CC Q14973; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-3923031, EBI-4403649; CC Q14973; Q9Y6D0: SELENOK; NbExp=3; IntAct=EBI-3923031, EBI-9679163; CC Q14973; Q8WV19: SFT2D1; NbExp=3; IntAct=EBI-3923031, EBI-2854842; CC Q14973; O95562: SFT2D2; NbExp=3; IntAct=EBI-3923031, EBI-4402330; CC Q14973; Q9H9B4: SFXN1; NbExp=3; IntAct=EBI-3923031, EBI-355861; CC Q14973; Q9Y666-2: SLC12A7; NbExp=3; IntAct=EBI-3923031, EBI-12854384; CC Q14973; Q7RTY0: SLC16A13; NbExp=3; IntAct=EBI-3923031, EBI-12243266; CC Q14973; Q96AG3: SLC25A46; NbExp=3; IntAct=EBI-3923031, EBI-10281975; CC Q14973; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-3923031, EBI-12867720; CC Q14973; Q9H2H9: SLC38A1; NbExp=3; IntAct=EBI-3923031, EBI-9978441; CC Q14973; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-3923031, EBI-10314552; CC Q14973; Q8IVJ1: SLC41A1; NbExp=3; IntAct=EBI-3923031, EBI-12266234; CC Q14973; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-3923031, EBI-3907610; CC Q14973; Q8WY07: SLC7A3; NbExp=3; IntAct=EBI-3923031, EBI-13066314; CC Q14973; O60906: SMPD2; NbExp=3; IntAct=EBI-3923031, EBI-12828299; CC Q14973; O15400: STX7; NbExp=3; IntAct=EBI-3923031, EBI-3221827; CC Q14973; Q03518: TAP1; NbExp=3; IntAct=EBI-3923031, EBI-747259; CC Q14973; P02786: TFRC; NbExp=3; IntAct=EBI-3923031, EBI-355727; CC Q14973; Q969X1: TMBIM1; NbExp=3; IntAct=EBI-3923031, EBI-2820569; CC Q14973; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-3923031, EBI-10171534; CC Q14973; Q9BTD3: TMEM121; NbExp=3; IntAct=EBI-3923031, EBI-12155101; CC Q14973; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-3923031, EBI-348587; CC Q14973; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-3923031, EBI-347385; CC Q14973; Q8WY98: TMEM234; NbExp=3; IntAct=EBI-3923031, EBI-8642211; CC Q14973; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-3923031, EBI-11528917; CC Q14973; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-3923031, EBI-10315004; CC Q14973; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-3923031, EBI-2852148; CC Q14973; Q71RG4: TMUB2; NbExp=3; IntAct=EBI-3923031, EBI-2820477; CC Q14973; Q96B49: TOMM6; NbExp=3; IntAct=EBI-3923031, EBI-10826510; CC Q14973; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-3923031, EBI-12195249; CC Q14973; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-3923031, EBI-11988865; CC Q14973; Q9NYZ1: TVP23B; NbExp=3; IntAct=EBI-3923031, EBI-11343401; CC Q14973; Q53HI1: UNC50; NbExp=3; IntAct=EBI-3923031, EBI-7601760; CC Q14973; Q15836: VAMP3; NbExp=3; IntAct=EBI-3923031, EBI-722343; CC Q14973; O95070: YIF1A; NbExp=3; IntAct=EBI-3923031, EBI-2799703; CC Q14973; Q9BSR8: YIPF4; NbExp=3; IntAct=EBI-3923031, EBI-751253; CC Q14973; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-3923031, EBI-751210; CC Q14973; Q96FB2; NbExp=3; IntAct=EBI-3923031, EBI-2857623; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14660639, CC ECO:0000269|PubMed:24867799}; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in liver (PubMed:11031103, CC PubMed:12409283). Expressed in placental trophoblasts CC (PubMed:12409283). {ECO:0000269|PubMed:11031103, CC ECO:0000269|PubMed:12409283, ECO:0000269|PubMed:9458785}. CC -!- DISEASE: Hypercholanemia, familial, 2 (FHCA2) [MIM:619256]: An CC autosomal recessive inborn error of metabolism characterized by CC persistently increased plasma levels of conjugated bile salts apparent CC from infancy, fat malabsorption and impaired absorption of fat-soluble CC vitamins, including D and K. Most patients are asymptomatic. Some CC neonates may have transient jaundice or transiently elevated liver CC enzymes. {ECO:0000269|PubMed:14660639, ECO:0000269|PubMed:24867799, CC ECO:0000269|PubMed:27882152, ECO:0000269|PubMed:28283843, CC ECO:0000269|PubMed:28835676, ECO:0000269|PubMed:29290974, CC ECO:0000269|PubMed:31661128, ECO:0000269|PubMed:34369070}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the bile acid:sodium symporter (BASS) (TC CC 2.A.28) family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L21893; AAA36381.1; -; mRNA. DR EMBL; AY544127; AAT11158.1; -; mRNA. DR EMBL; CH471061; EAW81011.1; -; Genomic_DNA. DR EMBL; BC069799; AAH69799.1; -; mRNA. DR EMBL; BC069822; AAH69822.1; -; mRNA. DR EMBL; BC074724; AAH74724.1; -; mRNA. DR EMBL; BC126298; AAI26299.1; -; mRNA. DR EMBL; BC136355; AAI36356.1; -; mRNA. DR CCDS; CCDS9797.1; -. DR PIR; I55601; I55601. DR RefSeq; NP_003040.1; NM_003049.3. DR PDB; 7FCI; EM; 3.30 A; A=1-349. DR PDB; 7PQG; EM; 3.70 A; A=3-328. DR PDB; 7PQQ; EM; 3.30 A; A=3-328. DR PDB; 7VAD; EM; 3.41 A; A=1-319. DR PDB; 7VAG; EM; 3.32 A; A=1-319. DR PDB; 7WSI; EM; 3.32 A; A=1-319. DR PDB; 7ZYI; EM; 2.88 A; A=1-349. DR PDBsum; 7FCI; -. DR PDBsum; 7PQG; -. DR PDBsum; 7PQQ; -. DR PDBsum; 7VAD; -. DR PDBsum; 7VAG; -. DR PDBsum; 7WSI; -. DR PDBsum; 7ZYI; -. DR AlphaFoldDB; Q14973; -. DR SMR; Q14973; -. DR BioGRID; 112443; 100. DR IntAct; Q14973; 89. DR STRING; 9606.ENSP00000216540; -. DR BindingDB; Q14973; -. DR ChEMBL; CHEMBL5287; -. DR DrugBank; DB15248; Bulevirtide. DR DrugBank; DB00887; Bumetanide. DR DrugBank; DB02659; Cholic Acid. DR DrugBank; DB00286; Conjugated estrogens. DR DrugBank; DB00091; Cyclosporine. DR DrugBank; DB03619; Deoxycholic acid. DR DrugBank; DB00977; Ethinylestradiol. DR DrugBank; DB02123; Glycochenodeoxycholic Acid. DR DrugBank; DB00328; Indomethacin. DR DrugBank; DB00279; Liothyronine. DR DrugBank; DB01583; Liotrix. DR DrugBank; DB08860; Pitavastatin. DR DrugBank; DB01032; Probenecid. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB14761; Remdesivir. DR DrugBank; DB01098; Rosuvastatin. DR DrugBank; DB06290; Simeprevir. DR DrugBank; DB04348; Taurocholic acid. DR DrugBank; DB00624; Testosterone. DR DrugBank; DB13943; Testosterone cypionate. DR DrugBank; DB13944; Testosterone enanthate. DR DrugBank; DB13946; Testosterone undecanoate. DR DrugBank; DB09100; Thyroid, porcine. DR DrugBank; DB01586; Ursodeoxycholic acid. DR DrugCentral; Q14973; -. DR GuidetoPHARMACOLOGY; 959; -. DR TCDB; 2.A.28.1.9; the bile acid:na(+) symporter (bass) family. DR GlyCosmos; Q14973; 4 sites, No reported glycans. DR GlyGen; Q14973; 4 sites. DR iPTMnet; Q14973; -. DR PhosphoSitePlus; Q14973; -. DR BioMuta; SLC10A1; -. DR DMDM; 2498046; -. DR MassIVE; Q14973; -. DR PaxDb; Q14973; -. DR PeptideAtlas; Q14973; -. DR Antibodypedia; 47330; 227 antibodies from 28 providers. DR DNASU; 6554; -. DR Ensembl; ENST00000216540.5; ENSP00000216540.4; ENSG00000100652.5. DR GeneID; 6554; -. DR KEGG; hsa:6554; -. DR MANE-Select; ENST00000216540.5; ENSP00000216540.4; NM_003049.4; NP_003040.1. DR UCSC; uc001xlr.3; human. DR AGR; HGNC:10905; -. DR CTD; 6554; -. DR DisGeNET; 6554; -. DR GeneCards; SLC10A1; -. DR HGNC; HGNC:10905; SLC10A1. DR HPA; ENSG00000100652; Tissue enriched (liver). DR MalaCards; SLC10A1; -. DR MIM; 182396; gene. DR MIM; 619256; phenotype. DR neXtProt; NX_Q14973; -. DR OpenTargets; ENSG00000100652; -. DR Orphanet; 238475; Familial hypercholanemia. DR PharmGKB; PA317; -. DR VEuPathDB; HostDB:ENSG00000100652; -. DR eggNOG; KOG2718; Eukaryota. DR GeneTree; ENSGT00950000182808; -. DR HOGENOM; CLU_034788_7_5_1; -. DR InParanoid; Q14973; -. DR OMA; MEIGIHN; -. DR OrthoDB; 3035577at2759; -. DR PhylomeDB; Q14973; -. DR TreeFam; TF315811; -. DR PathwayCommons; Q14973; -. DR Reactome; R-HSA-159418; Recycling of bile acids and salts. DR SignaLink; Q14973; -. DR BioGRID-ORCS; 6554; 9 hits in 1144 CRISPR screens. DR ChiTaRS; SLC10A1; human. DR GeneWiki; SLC10A1; -. DR GenomeRNAi; 6554; -. DR Pharos; Q14973; Tclin. DR PRO; PR:Q14973; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q14973; protein. DR Bgee; ENSG00000100652; Expressed in liver and 89 other tissues. DR Genevisible; Q14973; HS. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008508; F:bile acid:sodium symporter activity; IBA:GO_Central. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0015721; P:bile acid and bile salt transport; IBA:GO_Central. DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0120188; P:regulation of bile acid secretion; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR Gene3D; 1.20.1530.20; -; 1. DR InterPro; IPR002657; BilAc:Na_symport/Acr3. DR InterPro; IPR004710; Bilac:Na_transpt. DR InterPro; IPR038770; Na+/solute_symporter_sf. DR PANTHER; PTHR10361; SODIUM-BILE ACID COTRANSPORTER; 1. DR PANTHER; PTHR10361:SF40; SODIUM/BILE ACID COTRANSPORTER; 1. DR Pfam; PF01758; SBF; 1. DR TIGRFAMs; TIGR00841; bass; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disease variant; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; Ion transport; KW Lipid transport; Membrane; Receptor; Reference proteome; Sodium; KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..349 FT /note="Hepatic sodium/bile acid cotransporter" FT /id="PRO_0000052335" FT TRANSMEM 25..45 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 60..80 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 91..111 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 120..140 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 156..176 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 191..211 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 220..240 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 283..303 FT /note="Helical" FT /evidence="ECO:0000255" FT CARBOHYD 5 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 11 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 117 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 336 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 21 FT /note="R -> C (decreased function in taurocholate FT transport; dbSNP:rs200758433)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085560" FT VARIANT 39 FT /note="M -> T (decreased function in taurocholate FT transport; dbSNP:rs536458730)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085561" FT VARIANT 41 FT /note="S -> L (decreased function in taurocholate FT transport; dbSNP:rs111885789)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085562" FT VARIANT 64 FT /note="A -> T (decreased function in taurocholate FT transport; dbSNP:rs202018997)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085563" FT VARIANT 73 FT /note="P -> T (severely decreased function in taurocholate FT transport; dbSNP:rs763683476)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085564" FT VARIANT 88 FT /note="I -> T (in FHCA2; decreased function in taurocholate FT transport; dbSNP:rs148467625)" FT /evidence="ECO:0000269|PubMed:29290974, FT ECO:0000269|PubMed:32101444, ECO:0000269|PubMed:34369070" FT /id="VAR_085565" FT VARIANT 138 FT /note="L -> P (loss of function in taurocholate transport; FT dbSNP:rs543063679)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085566" FT VARIANT 159 FT /note="I -> M (decreased function in taurocholate FT transport; dbSNP:rs144006534)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085567" FT VARIANT 180 FT /note="R -> Q (decreased function in taurocholate FT transport; dbSNP:rs571796903)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085568" FT VARIANT 190 FT /note="G -> E (decreased function in taurocholate FT transport; dbSNP:rs553948182)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085569" FT VARIANT 199 FT /note="S -> R (in FHCA2; dbSNP:rs746174545)" FT /evidence="ECO:0000269|PubMed:31661128, FT ECO:0000269|PubMed:34369070" FT /id="VAR_085570" FT VARIANT 223 FT /note="I -> T (decreased transport of taurocholate and FT cholate; decreased transport of estron sulfate; decreased FT expression at the cell membrane due to intracellular FT retention; dbSNP:rs61745930)" FT /evidence="ECO:0000269|PubMed:14660639" FT /id="VAR_085571" FT VARIANT 232 FT /note="I -> T (slightly decreased function in taurocholate FT transport; dbSNP:rs190268737)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085572" FT VARIANT 234 FT /note="F -> L (severely decreased function in taurocholate FT transport; dbSNP:rs139931299)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085573" FT VARIANT 241 FT /note="S -> F (loss of function in taurocholate transport; FT dbSNP:rs150579813)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085574" FT VARIANT 249 FT /note="R -> W (severely decreased function in taurocholate FT transport; dbSNP:rs76966244)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085575" FT VARIANT 252 FT /note="R -> C (severely decreased function in taurocholate FT transport; dbSNP:rs141269120)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085576" FT VARIANT 252 FT /note="R -> H (in FHCA2; loss of function in taurocholate FT transport; loss of localization to the cell membrane due to FT intracellular retention; dbSNP:rs147226818)" FT /evidence="ECO:0000269|PubMed:24867799" FT /id="VAR_085577" FT VARIANT 252 FT /note="R -> S (severely decreased function in taurocholate FT transport; dbSNP:rs141269120)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085578" FT VARIANT 258 FT /note="T -> S (decreased function in taurocholate FT transport; dbSNP:rs541801766)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085579" FT VARIANT 267 FT /note="S -> F (in FHCA2; associated with resistance to FT hepatitis B virus infection and chronic hepatitis; unable FT to transport taurocholate and cholate; does not affect FT uptake of estrone sulfate; does not affect localization to FT the cell membrane; dbSNP:rs2296651)" FT /evidence="ECO:0000269|PubMed:14660639, FT ECO:0000269|PubMed:25418280, ECO:0000269|PubMed:27882152, FT ECO:0000269|PubMed:28283843, ECO:0000269|PubMed:28835676, FT ECO:0000269|PubMed:29290974, ECO:0000269|PubMed:31661128, FT ECO:0000269|PubMed:34369070" FT /id="VAR_022113" FT VARIANT 279 FT /note="I -> T (decreased transport of taurocholate and FT cholate; decreased transport of estron sulfate; does not FT affect localization to the cell membrane; FT dbSNP:rs72547507)" FT /evidence="ECO:0000269|PubMed:14660639, FT ECO:0000269|PubMed:32101444" FT /id="VAR_085580" FT VARIANT 293 FT /note="Q -> E (decreased function in taurocholate FT transport; dbSNP:rs189313778)" FT /evidence="ECO:0000269|PubMed:32101444" FT /id="VAR_085581" FT VARIANT 314 FT /note="K -> E (decreased transport of taurocholate and FT cholate; decreased transport of estron sulfate; does not FT affect localization to the cell membrane; FT dbSNP:rs72547506)" FT /evidence="ECO:0000269|PubMed:14660639" FT /id="VAR_085582" FT HELIX 16..20 FT /evidence="ECO:0007829|PDB:7VAG" FT HELIX 21..42 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 43..45 FT /evidence="ECO:0007829|PDB:7PQQ" FT HELIX 48..56 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 59..70 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 72..82 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 87..97 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 104..111 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 116..142 FT /evidence="ECO:0007829|PDB:7FCI" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:7FCI" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:7PQQ" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:7PQQ" FT HELIX 156..179 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 181..215 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 220..243 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 248..259 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 264..273 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 276..279 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 280..284 FT /evidence="ECO:0007829|PDB:7FCI" FT HELIX 285..309 FT /evidence="ECO:0007829|PDB:7FCI" SQ SEQUENCE 349 AA; 38119 MW; F3AB2CC2FBD925E3 CRC64; MEAHNASAPF NFTLPPNFGK RPTDLALSVI LVFMLFFIML SLGCTMEFSK IKAHLWKPKG LAIALVAQYG IMPLTAFVLG KVFRLKNIEA LAILVCGCSP GGNLSNVFSL AMKGDMNLSI VMTTCSTFCA LGMMPLLLYI YSRGIYDGDL KDKVPYKGIV ISLVLVLIPC TIGIVLKSKR PQYMRYVIKG GMIIILLCSV AVTVLSAINV GKSIMFAMTP LLIATSSLMP FIGFLLGYVL SALFCLNGRC RRTVSMETGC QNVQLCSTIL NVAFPPEVIG PLFFFPLLYM IFQLGEGLLL IAIFWCYEKF KTPKDKTKMI YTAATTEETI PGALGNGTYK GEDCSPCTA //